Despite advances in antiretroviral therapy and access to care, the HIV epidemic continues to grow. Historically, women have been poorly represented in HIV clinical trials even though almost half of the global HIV-infected population is female. Poor representation of women in clinical trials has led to the delay in accurate studies examining sex-specific differences in access to care, treatment outcomes and adherence. In developing countries, sex-specific differences are more evident than in developed countries, but no clear etiology for these differences has been identified. In the near future, novel agents for treatment-naive and treatment-experienced patients will be available. Strict monitoring and proper representation in clinical trials will be needed to allow the determination of sex-specific differences with these new agents.